Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles

Détails

ID Serval
serval:BIB_3A69FB387E5C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles
Périodique
American Journal of Physiology - Heart and Circulatory Physiology
Auteur(s)
Schafer  S. C., Wallerath  T., Closs  E. I., Schmidt  C., Schwarz  P. M., Forstermann  U., Lehr  H. A.
ISSN
0363-6135 (Print)
Statut éditorial
Publié
Date de publication
2005
Volume
288
Numéro
1
Pages
H436-H444
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
Long-term treatment with glucocorticoids is associated with mild to moderate hypertension. We reported previously that downregulation of endothelial NO synthase (eNOS) expression and activity is likely to contribute to this increase in blood pressure. In the present study, we tested the effects of dexamethasone on the vasodilation of microvascular arterioles using implanted dorsal skin-fold chambers in anesthetized C57BL/6J mice. Experiments were performed on control mice or on mice treated with dexamethasone (0.1-3 mg/kg of body wt). Endothelium-dependent vasodilation in response to ACh (0.1-10 microM) was reduced by dexamethasone in a dose-dependent fashion. Comparable inhibition was seen in tissues superfused with 30 microM N(G)-nitro-L-arginine methyl ester. In contrast, endothelium-independent vasodilation in response to S-nitroso-N-acetyl-D,L-penicillamine (10 microM) was not influenced by either dexamethasone or N(G)-nitro-L-arginine methyl ester. Levels of eNOS mRNA in murine hearts and NO(2)(-)/NO(3)(-) in serum were suppressed by dexamethasone (down to 63 and 50% of control values, respectively, at 3 mg/kg of body wt) along with a reduction in eNOS protein to 85.6%. Dexamethasone also concentration dependently reduced the expression of the cationic amino acid transporter-1 in murine hearts and cultured endothelial cells. The suppression by dexamethasone of the ACh-induced vasodilation could be partially reversed by dietary L-arginine (50 mg/kg of body wt) and by dietary vitamin C (10 g/kg of diet). We conclude that suppression by dexamethasone of the endothelium-mediated microvascular vasodilation involves several mechanisms including 1) downregulation of eNOS, 2) downregulation of cationic amino acid transporter-1, and 3) generation of reactive oxygen species. The demonstration that L-arginine and vitamin C can partially offset the effects of dexamethasone on microvascular arterioles suggests the potential clinical usefulness of these agents for the reduction of glucocorticoid-induced hypertension
Mots-clé
Acetylcholine/pharmacology/Animals/Antioxidants/Arginine/Arterioles/drug effects/metabolism/physiology/Ascorbic Acid/Cationic Amino Acid Transporter 1/antagonists & inhibitors/Cells,Cultured/Dexamethasone/Endothelial Cells/Glucocorticoids/Humans/Mice/Mice,Inbred C57BL/Myocardium/Nitrates/blood/Nitric Oxide Synthase/Nitric Oxide Synthase Type II/Nitric Oxide Synthase Type III/Nitrites/Oxidative Stress/Vascular Resistance/Vasodilation
Pubmed
Web of science
Création de la notice
29/01/2008 19:35
Dernière modification de la notice
20/08/2019 14:30
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